CAJ | 학술논문

目的制作2型糖尿病大鼠模型,观察肾小管间质损伤是否为2型糖尿病的早期肾脏病理改变并探讨其干预方法及可能的机制.方法采用高糖高脂饮食诱导联合小剂量链脲佐菌素(STZ)的方法建立2型糖尿病模型,同时设立正常对照组,采用肾康注射液(SKI)进行治疗,观察大鼠的一般状态、生化指标、尿微量白蛋白及尿N-乙酰-β-氨基葡萄糖苷酶(NAG)的改变;应用高胰岛素-正葡萄糖钳夹实验评估大鼠的胰岛素抵抗情况,肾组织高碘酸-雪夫染色(PAS染色)反应观察其病理变化;应用免疫组化方法检测肾组织Toll样受体4(TLR4)表达及肾间质CD68+细胞数.结果糖尿病大鼠体质量减轻,尿微量白蛋白和尿NAG明显升高,胰岛素抵抗明显,肾小球体积增大,肾小管广泛空泡样变性,肾组织TLR4表达及肾间质CD68+细胞数明显增加[TLR4的累积吸光度(A)值:6 289.86±272.45与207.14-22.37,CD68+细胞数:8.79±0.79与1.23±0.52],SKI治疗后上述情况均有不同程度改善(均P ＜0.05).结论肾小管间质病变是2型糖尿病早期肾损害表现,SKI可以减轻肾脏的损伤,其机制可能与减少肾组织TLR4表达,抑制炎症介导的巨噬细胞浸润有关.
목적 제작2형당뇨병대서모형,관찰신소관간질손상시부위2형당뇨병적조기신장병리개변병탐토기간예방법급가능적궤제.방법 채용고당고지음식유도연합소제량련뇨좌균소(STZ)적방법건립2형당뇨병모형,동시설립정상대조조,채용신강주사액(SKI)진행치료,관찰대서적일반상태、생화지표、뇨미량백단백급뇨N-을선-β-안기포도당감매(NAG)적개변;응용고이도소-정포도당겸협실험평고대서적이도소저항정황,신조직고전산-설부염색(PAS염색)반응관찰기병리변화;응용면역조화방법검측신조직Toll양수체4(TLR4)표체급신간질CD68+세포수.결과 당뇨병대서체질량감경,뇨미량백단백화뇨NAG명현승고,이도소저항명현,신소구체적증대,신소관엄범공포양변성,신조직TLR4표체급신간질CD68+세포수명현증가[TLR4적루적흡광도(A)치:6 289.86±272.45여207.14-22.37,CD68+세포수:8.79±0.79여1.23±0.52],SKI치료후상술정황균유불동정도개선(균P ＜0.05).결론 신소관간질병변시2형당뇨병조기신손해표현,SKI가이감경신장적손상,기궤제가능여감소신조직TLR4표체,억제염증개도적거서세포침윤유관.
Objective To explore whether renal tubulointerstitial lesions are early renal pathological changes and its interventions in diabetic rats.Methods The type 2 diabetic rat model was induced by a high-sugar and high-fat diet with a low-dose intraperitoneal injection of streptozotocin.And Shenkang Injection (SKI) was used as an intervention drug.A total of 30 Sprague-Dawley rats were divided randomly into diabetic (DM),DM + SKI (DMSK) and normal control (NC) groups.The general status,blood biochemical parameters,microalbuminuria and urinary N-acetyl-D-glueosaminidas (NAG) were recorded.The insulin resistance of diabetic rats was detected with hyperinsulinemic-euglycemic clamp test.Renal pathological changes were evaluated with periodic acid-Schiff (PAS) staining.The expression of Toll-like receptor 4 (TLR4) in kidney tissue and renal interstitial CD68+ cells was detected with immunohistochemistry.Results The levels of microalbuminuria,urinary NAG,glomerular volume,renal tubular score,TLR4 expression and renal interstitial CD68 + cells significantly increased in DM rats with body weight loss and insulin resistance (IOD value of TLR4:6 289.86 ± 272.45 vs 207.14 ± 22.37 ; CD68 + cells:8.79 ± 0.79 vs.1.23 ± 0.52).All changes in DM rats improved after SKI intervention (P ＜ 0.05).Conclusion Renal tubulointerstitial lesions are early renal damages in type 2 diabetic rats.SKI can attenuate diabetic tubulointerstitial damage and delay the progression of diabetic nephropathy associated with the inhibition of TLR4 expression and inflammation-mediated macrophage infiltration.